dbSNP rs3124955: FCN2:c.214+60T>C (chr9-134882699-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004108.3(FCN2):c.214+60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,207,266 control chromosomes in the GnomAD database, including 75,866 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8131 hom., cov: 32)

Exomes 𝑓: 0.36 ( 67735 hom. )

Consequence

FCN2
NM_004108.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.19

Publications

8 publications found

Variant links:

Genes affected

FCN2 (HGNC:3624): (ficolin 2) The product of this gene belongs to the ficolin family of proteins. This family is characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. This gene is predominantly expressed in the liver, and has been shown to have carbohydrate binding and opsonic activities. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

FCN2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004108.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	NM_004108.3	MANE Select	c.214+60T>C		intron	N/A	NP_004099.2	Q15485-1
	FCN2	NM_015837.3		c.101-603T>C		intron	N/A	NP_056652.1	Q15485-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FCN2	ENST00000291744.11	TSL:1 MANE Select	c.214+60T>C	intron	N/A	ENSP00000291744.6	Q15485-1
FCN2	ENST00000855732.1		c.214+60T>C	intron	N/A	ENSP00000525791.1
FCN2	ENST00000855735.1		c.214+60T>C	intron	N/A	ENSP00000525794.1

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48825

AN:

151768

Hom.:

8123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.442

Gnomad EAS

AF:

0.434

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.354

GnomAD4 exome

AF:

0.357

AC:

377017

AN:

1055380

Hom.:

67735

AF XY:

0.360

AC XY:

194455

AN XY:

540280

show subpopulations

African (AFR)

AF:

0.248

AC:

6356

AN:

25608

American (AMR)

AF:

0.271

AC:

11553

AN:

42638

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

10289

AN:

22866

East Asian (EAS)

AF:

0.407

AC:

15342

AN:

37738

South Asian (SAS)

AF:

0.429

AC:

32893

AN:

76722

European-Finnish (FIN)

AF:

0.367

AC:

18184

AN:

49602

Middle Eastern (MID)

AF:

0.413

AC:

2053

AN:

4968

European-Non Finnish (NFE)

AF:

0.352

AC:

263111

AN:

748440

Other (OTH)

AF:

0.368

AC:

17236

AN:

46798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

12215

24430

36646

48861

61076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7268

14536

21804

29072

36340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.322

AC:

48837

AN:

151886

Hom.:

8131

Cov.:

AF XY:

0.322

AC XY:

23913

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.243

AC:

10080

AN:

41410

American (AMR)

AF:

0.307

AC:

4685

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.442

AC:

1532

AN:

3466

East Asian (EAS)

AF:

0.433

AC:

2227

AN:

5146

South Asian (SAS)

AF:

0.436

AC:

2099

AN:

4818

European-Finnish (FIN)

AF:

0.371

AC:

3911

AN:

10546

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.343

AC:

23258

AN:

67904

Other (OTH)

AF:

0.359

AC:

757

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1659

3319

4978

6638

8297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.330

Hom.:

2998

Bravo

AF:

0.315

Asia WGS

AF:

0.419

AC:

1455

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.16

(source)

DANN

Benign

0.36

PhyloP100

-3.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over